Targeting enteroviral 2A protease by a 16-mer synthetic peptide: Inhibition of 2Apro-induced apoptosis in a stable Tet-on HeLa cell line

AbstractEnteroviridae such as coxsackievirus are important infectious agents causing viral heart diseases. Viral protease 2A (2Apro) initiates the virus life cycle, and is an excellent target for developing antiviral drugs. Here, to evaluate the validity of the 2Apro as a proper therapeutic target, and based on the existing information and molecular dynamics, a 16-mer peptide was designed to specifically target the active site of protease 2Apro in order to block the activity of CVB3 2Apro. We showed that the peptide could compete with endogenous substrate in a concentration-dependent manner. Further, we established a HeLa cell line that expressed 2Apro. Expression of 2Apro resulted in significant morphological alteration and eventual cell death. Western blot and viability assay showed that the 16-mer peptide (200 μg/ml) could significantly block 2Apro activity and its cytotoxic effect. Future modification of the 16-mer peptide can improve its affinity for 2Apro and therefore develop effective antiviral drug

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Pros and Cons of Informed Consent in Gynecology and Obstetrics

Obtaining informed consent is a fundamental aspect of medical ethics to protect patients’ autonomy and human dignity. An adequate practice of informed consent is complex and has not only personal but also ethical, legal, and administrative implications

Wheat Germ Fermentation with Saccharomyces cerevisiae and Lactobacillus plantarum: Process Optimization for Enhanced Composition and Antioxidant Properties In Vitro

Wheat germ, a by-product of the flour milling industry, is currently commercialized mainly for animal feed applications. This study aims to explore and optimize the process of wheat germ fermentation to achieve products with enhanced nutritional composition and biological properties and further characterize the fermented products generated using these optimum conditions. The type of microorganism (Saccharomyces cerevisiae 5022 (yeast) and Lactobacillus plantarum strain 299v (bacteria)), pH (4.5, 6, and 7.5) and fermentation time (24, 48, and 72 h) were optimized using response surface methodology (RSM) aiming to achieve fermented products with high total phenol content (TPC), dimethoxy benzoquinone (DMBQ) and antioxidant activities. Optimum fermentation conditions were achieved using L. plantarum, pH 6, 48 h, generating extracts containing TPC (3.33 mg gallic acid equivalents/g), DMBQ (0.56 mg DMBQ/g), and DPPH radical scavenging (86.49%). These optimally fermented products had higher peptide concentrations (607 μg/mL), gamma-aminobutyric acid (GABA) (19,983.88 mg/kg) contents compared to non-fermented or yeast-fermented products. These findings highlight the influence of fermentation conditions of wheat germ and the promising industrial application of wheat germ fermentation for developing food products with enhanced biological properties promising for their commercialization as functional foods.Department of Agriculture, Food and the MarineEuropean Commission Horizon 202

A Fresh look at the male-specific region of the human Y chromosome

The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. This project attempts simultaneously to establish a sound basis for the development of diagnostic, prognostic, therapeutic, and preventive medical applications. In Iran, current efforts focus on mapping the proteome of the human Y chromosome. The male-specific region of the Y chromosome (MSY) is unique in many aspects and comprises 95% of the chromosome's length. The MSY continually retains its haploid state and is full of repeated sequences. It is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of MSY protein-encoding genes and their association with various traits and diseases including sex determination and reversal, spermatogenesis and male infertility, cancers such as prostate cancers, sex-specific effects on the brain and behavior, and graft-versus-host disease. We also present information available from RNA sequencing, protein-protein interaction, post-translational modification of MSY protein-coding genes and their implications in biological systems. An overview of Human Y chromosome Proteome Project is presented and a systematic approach is suggested to ensure that at least one of each predicted protein-coding gene's major representative proteins will be characterized in the context of its major anatomical sites of expression, its abundance, and its functional relevance in a biological and/or medical context. There are many technical and biological issues that will need to be overcome in order to accomplish the full scale mapping.17 page(s